Letter | Published:

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

Nature Genetics volume 42, pages 224228 (2010) | Download Citation

Abstract

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10−11, per-allele odds ratio (OR) 1.26, 95% CI 1.18–1.35) and rs9564966 (P = 5.86 × 10−8, per-allele OR 1.21, 95% CI 1.13–1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10−10, per-allele OR 0.77, 95% CI 0.71–0.84). A single SNP, rs401681 (P = 3.66 × 10−7, per-allele OR 1.19, 95% CI 1.11–1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

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Acknowledgements

The authors gratefully acknowledge the energy and contribution of our late colleague Sheila Bingham. Additional acknowledgments are in the Supplementary Note.

Author information

Author notes

    • Gloria M Petersen
    • , Laufey Amundadottir
    • , Charles S Fuchs
    • , Peter Kraft
    • , Rachael Z Stolzenberg-Solomon
    • , Robert N Hoover
    • , Patricia Hartge
    •  & Stephen J Chanock

    These authors contributed equally to this work.

Affiliations

  1. Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

    • Gloria M Petersen
    • , William R Bamlet
    • , Mariza de Andrade
    •  & Robert R McWilliams
  2. Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

    • Laufey Amundadottir
    • , Hemang Parikh
    •  & Stephen J Chanock
  3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland, USA.

    • Laufey Amundadottir
    • , Rachael Z Stolzenberg-Solomon
    • , Kevin B Jacobs
    • , Demetrius Albanes
    • , Amy Hutchinson
    • , Julie B Mendelsohn
    • , Hemang Parikh
    • , Gilles Thomas
    • , Geoffrey S Tobias
    • , Zhaoming Wang
    • , Kai Yu
    • , Joseph F Fraumeni Jr
    • , Robert N Hoover
    • , Patricia Hartge
    •  & Stephen J Chanock
  4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

    • Charles S Fuchs
    •  & Brian M Wolpin
  5. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Charles S Fuchs
    • , Edward L Giovannucci
    • , Susan E Hankinson
    • , David J Hunter
    •  & Brian M Wolpin
  6. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Peter Kraft
    • , Edward L Giovannucci
    • , Susan E Hankinson
    • , David J Hunter
    • , Dominique S Michaud
    •  & Dimitrios Trichopoulos
  7. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Peter Kraft
  8. Core Genotyping Facility, SAIC-Frederick Inc., National Cancer Institute-Frederick, Frederick, Maryland, USA.

    • Kevin B Jacobs
    • , Amy Hutchinson
    •  & Zhaoming Wang
  9. Bioinformed Consulting Services, Gaithersburg, Maryland, USA.

    • Kevin B Jacobs
  10. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.

    • Alan A Arslan
  11. Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.

    • Alan A Arslan
    •  & Anne Zeleniuch-Jacquotte
  12. New York University Cancer Institute, New York, New York, USA.

    • Alan A Arslan
    •  & Anne Zeleniuch-Jacquotte
  13. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands and Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands.

    • H Bas Bueno-de-Mesquita
  14. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

    • Steven Gallinger
  15. Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

    • Myron Gross
  16. Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA.

    • Kathy Helzlsouer
  17. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

    • Elizabeth A Holly
    •  & Paige M Bracci
  18. Department of Epidemiology, American Cancer Society, Atlanta, Georgia, USA.

    • Eric J Jacobs
    •  & Alpa V Patel
  19. Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Alison P Klein
  20. Department of Epidemiology, Bloomberg School of Public Health, The Sol Goldman Pancreatic Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

    • Alison P Klein
  21. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Andrea LaCroix
    • , Margaret T Mandelson
    •  & Charles Kooperberg
  22. Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

    • Donghui Li
    •  & Manal Hassan
  23. Group Health Center for Health Studies, Seattle, Washington, USA.

    • Margaret T Mandelson
  24. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Sara H Olson
  25. Yale University School of Public Health, New Haven, Connecticut, USA.

    • Harvey A Risch
    •  & Herbert Yu
  26. Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.

    • Wei Zheng
    •  & Xiao-Ou Shu
  27. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Christine D Berg
  28. Inserm, Paris-Sud University, Institut Gustave-Roussy, Villejuif, France.

    • Marie-Christine Boutron-Ruault
  29. Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Julie E Buring
  30. Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA.

    • Julie E Buring
  31. German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Federico Canzian
    •  & Rudolf Kaaks
  32. Johns Hopkins Bloomberg School of Public Health, George W. Comstock Center for Public Health Research and Prevention, Hagerstown, Maryland, USA.

    • Sandra Clipp
  33. Cancer Care Ontario and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

    • Michelle Cotterchio
  34. Catalan Institute of Oncology (ICO), Barcelona, Spain.

    • Eric J Duell
    •  & Mazda Jenab
  35. Physicians' Health Study, Divisions of Aging, Cardiovascular Disease, and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • J Michael Gaziano
  36. Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.

    • J Michael Gaziano
  37. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Edward L Giovannucci
  38. Departments of Oncology, Pathology and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Michael Goggins
  39. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.

    • Göran Hallmans
  40. MedStar Research Institute, Georgetown University, Hyattsville, Maryland, USA.

    • Barbara Howard
  41. Nutritional Epidemiology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumoridi Milano, Milan, Italy.

    • Vittorio Krogh
  42. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Robert C Kurtz
  43. Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA.

    • Shannon M Lynch
    •  & Daniela Seminara
  44. Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK.

    • Dominique S Michaud
    • , Petra H M Peeters
    •  & Elio Riboli
  45. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

    • Petra H M Peeters
  46. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Aleksandar Rajkovic
  47. Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain.

    • Laudina Rodriguez
  48. Synergie-Lyon-Cancer, Inserm, Centre Leon Berard, Lyon, Cedex, France.

    • Gilles Thomas
  49. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.

    • Anne Tjønneland
  50. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.

    • Dimitrios Trichopoulos
  51. Division of Research, Kaiser Permanente, Northern California Region, Oakland, California, USA.

    • Stephen K Van Den Eeden
  52. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Jarmo Virtamo
  53. Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.

    • Jean Wactawski-Wende

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Contributions

G.M.P., L.A., C.S.F., P.K., R.Z.S.-S., K.B.J., S.M.L., J.B.M., G.S.T., R.N.H., P.H. and S.J.C. organized and designed the study. L.A., A.H., K.B.J., G.T. and S.J.C. supervised genotyping of samples. L.A., P.K., R.Z.S.-S., C.S.F., K.B.J., C.K., H.P., Z.W., K.Y., R.N.H., P.H. and S.J.C. contributed to the design and execution of statistical analysis. L.A., G.M.P., P.K., R.Z.S.-S., R.N.H., P.H. and S.J.C. wrote the first draft of the manuscript. G.M.P., C.S.F., R.Z.S.-S., A.A.A., H.B.B., S.G., M.G., K.H., E.A.H., E.J.J., A.P.K., A.L., D.L., M.T.M., S.H.O., H.A.R., W.Z., D.A., W.R.B., C.D.B., M.-C.B.-R., J.E.B., P.M.B., F.C., S.C., M.C., M.deA., E.J.D., J.M.G., E.L.G., M.G., G.H., S.E.H., M.H., B.H., D.J.H., M.J., R.K., V.K., R.C.K., R.R.M., D.S.M., A.V.P., P.H.M.P., A.R., E.R., L.R., X.-O.S., A.T., D.T., S.K.V.D.E., J.V., J.W.-W., B.M.W., H.Y., A.Z.-J. and J.F.F.Jr. conducted the epidemiologic studies and contributed samples to the PanScan GWAS and/or replication. All authors contributed to the writing of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stephen J Chanock.

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https://doi.org/10.1038/ng.522

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